Tablet Of Paracetamol Containing An Encapsulated Flavorant

ABSTRACT

A medicament tablet containing paracetamol (acetaminophen) as the (or an) active ingredient, and an encapsulated flavorant. The tablet may be swallowed in tablet form or may be dissolved or dispersed in water to form a palatable drink.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 12/295,771, filed 27 Apr. 2009, which is a US National Stage of International Application No. PCT/GB2007/001202, filed 2 Apr. 2007, which claims the benefit of GB 0606848.0, filed 5 Apr. 2006, the entire contents and substance of which are each hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of Invention

This invention relates to a medicament product, and in particular to a compressed medicament tablet. The invention further relates to a method of manufacturing a compressed medicament tablet.

2. Background and Related Art

A number of commercially available analgesic products are flavored. Among such products commercially available in the UK are BOOTS Cold Relief Hot Blackcurrant/Lemon and the LEMSIP range from Reckitt Benckiser (registered trademarks). Analgesic products flavored with fruit flavorants, especially those reproducing sharp flavors such as blackcurrant and lemon, have excellent consumer acceptance.

However the incorporation of flavorants is not absolutely straightforward. Most flavorants are oil-based and are moderately volatile. Many tablets are made by a process which includes wet granulation, involving a drying step. If an oil-based flavorant is present during the drying step it may be lost, completely or in part. Furthermore, when analgesic tablets contain paracetamol as the (or an) active ingredient the process is inherently difficult; paracetamol is, simply, a difficult material to tablet. When an oil-based flavorant is added to paracetamol, it tends to increase the difficulties in tabletting; the oleophilic qualities of the flavorant act to increase the difficulty in getting particles to adhere together.

Thus, in an internet article called “New Opportunities—Speciality Pregelatinised Starch Excipients” by Dr F Heinze, at: www.samedanltd.com/members/archives/PMPS/Autumn2002/FredHeinze.htm Dr. Heinze states “Wet granulation is the chosen method for poorly compressible drugs such as Acetaminophen (paracetamol)”.

Additionally, U.S. Pat. No. 4,562,024 concerns an improved wet granulation process for preparing compressed tablets, particularly those containing a “poorly compressible medicament e.g. paracetamol”.

In the British Pharmaceutical Society (BPS) 2005 Science Abstracts, Abstract 212 which is available online at www.rpsgb.org.uk/pdfs/bpc05sciabs204-212.pdf; called “An Investigation into the Recrystallization Behaviour of Amorphous Paracetamol”, the authors S. Qi and D. Q. M. Craig, of the School of Chemical Sciences and Pharmacy, University of East Anglia, UK, state that paracetamol is known to exist in three polymorphic forms, including the stable monoclinic form I which has “poor tabletting properties”.

DETAILED DESCRIPTION OF THE INVENTION

To facilitate an understanding of the principles and features of the various embodiments of the invention, various illustrative embodiments are explained below. Although exemplary embodiments of the invention are explained in detail, it is to be understood that other embodiments are contemplated. Accordingly, it is not intended that the invention is limited in its scope to the details of construction and arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or carried out in various ways. Also, in describing the exemplary embodiments, specific terminology will be resorted to for the sake of clarity.

It must also be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. For example, reference to a component is intended also to include composition of a plurality of components. References to a composition containing “a” constituent is intended to include other constituents in addition to the one named.

Also, in describing the exemplary embodiments, terminology will be resorted to for the sake of clarity. It is intended that each term contemplates its broadest meaning as understood by those skilled in the art and includes all technical equivalents which operate in a similar manner to accomplish a similar purpose.

Ranges may be expressed herein as from “about” or “approximately” or “substantially” one particular value and/or to “about” or “approximately” or “substantially” another particular value. When such a range is expressed, other exemplary embodiments include from the one particular value and/or to the other particular value.

Similarly, as used herein, “substantially free” of something, or “substantially pure”, and like characterizations, can include both being “at least substantially free” of something, or “at least substantially pure”, and being “completely free” of something, or “completely pure”.

By “comprising” or “containing” or “including” is meant that at least the named compound, element, particle, or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, method steps, even if the other such compounds, material, particles, method steps have the same function as what is named.

It is also to be understood that the mention of one or more method steps does not preclude the presence of additional method steps or intervening method steps between those steps expressly identified. Similarly, it is also to be understood that the mention of one or more components in a composition does not preclude the presence of additional components than those expressly identified.

The materials described as making up the various elements of the invention are intended to be illustrative and not restrictive. Many suitable materials that would perform the same or a similar function as the materials described herein are intended to be embraced within the scope of the invention. Such other materials not described herein can include, but are not limited to, for example, materials that are developed after the time of the development of the invention.

Starting points for the present invention are that paracetamol is difficult to tablet, and that paracetamol tablets are conventionally made by a wet granulation process; consequently flavorants are difficult to incorporate. Adding them too early in the manufacturing process causes loss of flavorant.

In accordance with a first aspect of the present invention there is provided a medicament tablet containing paracetamol as the (or an) active ingredient, and an encapsulated flavorant.

Encapsulated flavorants are commercially available. It is known that they may assist in giving a product a longer shelf-life. We have realized, and shown, that when an encapsulated flavorant is used there is much greater flexibility in terms of the manufacturing process for a paracetamol medicament.

For example, when an encapsulated flavorant is used it may be added at any stage, even when wet granulation is carried out. That is, it can withstand the drying step which is needed, without loss or damage.

However, by use of a suitable encapsulated flavor and other ingredients, direct tabletting may be employed (and is preferred), without granulation taking place at all. That is to say, as-supplied ingredients (which may generally be in the form of powders but with the flavorant being in its encapsulated particulate form) may be mixed, then pressed. We have found that tablets of good mechanical properties can be obtained in this way.

In accordance with a second aspect of the present invention there is provided a method of making a tablet containing a paracetamol medicament, the method comprising the compression of powder or granular materials including paracetamol and an encapsulated flavorant.

Preferably the method comprises the direct compression of the ingredients.

Preferably the method does not include a heating or warming step.

Preferably the method does not include wet granulation.

Preferably a pressing aid is present. Especially preferred is a fatty acid or fatty acid ester, for example a stearate salt, preferably magnesium stearate.

Preferably the method includes the addition of an encapsulated flavorant substantially at the stage when paracetamol is mixed with the other ingredients.

In accordance with a third aspect of the present invention there is provided the use of an encapsulated flavorant in the manufacture of a paracetamol medicament.

The following statements and definitions apply to any or all of the first, second, third or fourth aspects of the present invention, as the context permits.

The encapsulated flavorant can with advantage be added with the other ingredients at the start of the mixing process (a substantial manufacturing advantage). The flavor sensation to the eventual customer may be good whether administered in drink form or in tablet form.

The tablets may contain a second analgesic medicament, of which favored examples are ibuprofen; flurbiprofen; buprenorphine; aspirin; codeine; celecoxib; diclofenac; ketoprofen; meloxicam; naproxen; and rofecoxib. Such compounds may be in the form stated or in the form of an optical isomer, salt or ester. For example ibuprofen may be in the form of ibuprofen acid, or in the form of an ibuprofen salt such as sodium ibuprofen, or lysine ibuprofen.

The paracetamol which is used may be coated with pre-gelatinized starch.

The tablet may contain a URT (upper respiratory tract) aid. A URT aid may be an active agent which assists in combating a cold, sore throat, cough or influenza. A URT aid include a decongestant, a cough suppressant (or antitussive), and an expectorant (or mucolytic agent). Suitable URT aids fulfilling one or more of the above-mentioned functions include: oxymetazoline, phenylephrine, pseudoephedrine, and diphenhydramine (examples of decongestants); dextromethorphan, noscapine, ethyl morphine, theobromine, pholcodine, and codeine (examples of cough suppressants); and guaifenesin and ambroxol (examples of expectorants). Such compounds may be in the form stated or in the form of an optical isomer, salt or ester. For example several of the compounds are commonly supplied in the form of their hydrochloride salt.

A preferred tablet of the present invention is one which is suitable to be swallowed in the tablet form but which also dissolves quickly in water to produce a palatable drink. Preferably the tablet can be swallowed in the tablet form without substantial or discomforting dissolution or disintegration in the mouth. Yet, preferably such a tablet dropped into a glass of water dissolves or disperses, with gentle stirring of the water, within 2 minutes, preferably within 1 minute, and most preferably within 30 seconds. Preferably this is the case when the water is at 60° C. (a reasonable reference test in relation to use to produce a hot drink). Preferably it also applies, alternatively or additionally, to water at 25° C. or 37° C., which some tests use as a reference temperature. Most preferably it dissolves or disperses within the stated time periods in water both at 25° C. or 37° C. or 60° C.

Preferably such a tablet contains a disintegration aid. The disintegration aid could be a material or materials that produce effervescence when the tablet is placed in water. Thus, the tablet could contain an effervescent couple, typically an ingestible acid and an ingestible base, which react together in water to liberate carbon dioxide. The liberated carbon dioxide assists in the break-up of the tablet. This type of disintegration aid is, of course, well known but is not the most preferred approach for the present invention, because it could produce undesirable effervescence in the saliva in the mouth, if a patient is slow to swallow the tablet.

Therefore, a more preferred disintegration type for use in this aspect of the invention is a non-effervescent disintegration aid; preferably a water-swellable material. Most preferred is a water-swellable polymer. A number of such materials are known, and are generally based on cross-linked polymers of N-vinyl-2-pyrrolidone compounds or on cellulosic compounds which have been chemically modified to enhance their water uptake capacity. Especially preferred are croscarmellose sodium or carboxymethylcellulose (SCMC), low-substituted hydroxypropylcellulose (L-HPC) and, especially, crospovidone.

Preferably the tablet contains a binder, for example a starch or cellulose derivative or a sugar alcohol. Many binders are known to the person skilled in the art but especially preferred for use in the tablets of the present invention is microcrystalline cellulose.

In addition to the encapsulated flavorant the tablet preferably contains a further flavoring agent, preferably an organic acid flavorant or salt thereof, non-encapsulated, for example citric acid, tartaric acid, malic acid, maleic acid, fumaric acid or ascorbic acid; or a salt of any of the foregoing (preferably an alkali metal salt). A polycarboxylic acid, preferably containing 2-4 carboxylic groups per molecule, is preferred; in particular citric acid.

In addition to the encapsulated flavorant and optionally a non-encapsulated organic acid flavorant or salt thereof the tablet preferably contains a further flavoring agent, in the form of a sweetening agent. A preferred sweetening agent is an intense synthetic or semi-synthetic sweetener, for example acesulfame potassium, sucralose, saccharin, neotame or, preferably, aspartame.

We have found, to our surprise, that when an encapsulated flavorant is employed it can be flavored in a way which is good when the tablet is to be swallowed as such, and which is also good when the tablet is dissolved in water to form a drink (for example a drink of volume 50-150 ml). We expected that the flavor would be too intense when the tablet was to be swallowed as such, and too weak in the drink form. Or, if one mode was formulated to be optimal, the other mode would be quite unsuitable. We were surprised to determine that the flavor sensation both in the tablet form and in the drink form was good; sufficiently good that the resulting tablet was one with a potential to be offered for sale, with a recommendation for both types of administration.

Preferably a tablet of the invention has a friability of up to 2%, preferably up to 1%, and most preferably up to 0.5%, as determined by Ph Eur monograph method 2.9.7.

Preferably a tablet of the invention has a hardness of at least 8 kp, preferably at least 10 kp, and most preferably at least 14 kp, as determined by Ph Eur monograph method 2.9.8.

Preferably a tablet of the invention has a hardness of up to 26 kp, preferably up to 22 kp, and most preferably up to 18 kp, as determined by Ph Eur monograph method 2.9.8.

Preferably a tablet of the invention is at least 700 mg in weight, preferably at least 780 mg, most preferably at least 860 mg.

Preferably a tablet of the invention is up to 1400 mg in weight, preferably up to 1200 mg, most preferably up to 1100 mg.

Preferably a tablet of the invention comprises at least 200 mg paracetamol, more preferably at least 300 mg, and most preferably at least 400 mg.

Preferably a tablet of the invention comprises up to 800 mg paracetamol, more preferably up to 700 mg, and most preferably up to 600 mg.

Most preferably the tablet contains 500-550 mg paracetamol.

Preferably a tablet of the invention comprises at least 40 mg of encapsulated flavorant, preferably at least 80 mg, preferably at least 100 mg.

Preferably a tablet of the invention comprises up to 240 mg of encapsulated flavorant, preferably up to 200 mg, preferably up to 150 mg.

When a URT aid is present it is preferably present in an amount of at least 2 mg, preferably at least 4 mg, most preferably at least 5 mg.

When a URT aid is present it is preferably present in an amount of up to 200 mg, preferably up to 100 mg, most preferably up to 50 mg, especially up to 30 mg.

When a disintegration aid is present it is preferably present in an amount of at least 20 mg, preferably at least 40 mg, most preferably at least 60 mg.

When a disintegration aid is present it is preferably present in an amount of up to 200 mg, preferably up to 140 mg, most preferably up to 100 mg.

When a binder is present it is preferably present in an amount of at least 20 mg, preferably at least 40 mg, most preferably at least 60 mg.

When a binder is present it is preferably present in an amount of up to 200 mg, preferably up to 140 mg, most preferably up to 100 mg.

When a pressing aid is present it is preferably present in an amount of at least 2 mg, preferably at least 4 mg, most preferably at least 5 mg.

When a pressing aid is present it is preferably present in an amount of up to 50 mg, preferably up to 20 mg, most preferably up to 10 mg.

When an organic acid or salt thereof is present as a further flavorant it is preferably in an amount of at least 10 mg, preferably at least 25 mg, most preferably at least 40 mg.

When an organic acid or salt thereof is present it is preferably present in an amount of up to 100 mg, preferably up to 80 mg, most preferably up to 60 mg.

When a sweetening agent is present it is preferably present in an amount of at least 10 mg, preferably at least 20 mg, most preferably at least 30 mg.

When a sweetening agent is present it is preferably present in an amount of up to 80 mg, preferably up to 65 mg, most preferably up to 50 mg.

In accordance with a fourth aspect of the present invention there is provided a medicament tablet comprising (and in a preferred embodiment consisting essentially of) the following components in the amounts stated:

paracetamol, 200-800 mg;

encapsulated flavorant, 40-240 mg;

disintegration aid, 20-200 mg;

binder, 20-200 mg;

pressing aid, 2-50 mg;

organic acid/salt flavorant, 10-100 mg; and

sweetening agent, 10-80 mg;

but in such amounts that the tablet weight is within the defined weight range; wherein the tablet has the following characteristics:

its weight is in the range 700-1400 mg;

its friability does not exceed 2% as determined by Ph Eur monograph method 2.9.7;

its hardness is in the range 8-26 kp as determined by Ph Eur monograph method 2.9.8;

it is palatable when taken as a tablet; and

it dissolves quickly in water to produce a palatable drink.

The tablet of the fourth aspect may additionally contain 2-200 mg of a URT aid.

There may be more than one component of a designated type; for example more than one URT aid, or more than one sweetening agent. In all such cases the amounts stated in the definitions and claims herein (for example binder, 20-200 mg; sweetening agent, 10-80 mg) represent the summation of such components.

The invention will now be further described, by way of example only.

In relation to the encapsulated flavorant we do not believe that the nature of the encapsulation is critical. Rather, we believe that the most important thing is simply the fact that the flavorant is encapsulated; and so is segregated from the paracetamol, and preferably from the other components of the tablet mentioned herein.

Thus we do not believe the chemical nature of the encapsulant to be critical to this invention. We believe that there are many disclosures of encapsulated flavorants which would be suitable, and of methods of making them. The nature of the encapsulated flavorant is not of the essence of this invention. Reference may be made to published patent specifications if further information is desired. Broadly, all encase the flavor source in a shell or compound it in a matrix, which is then comminuted to form particulate material.

The flavor ingredient encapsulated is preferably a hydrophobic flavor ingredient or composition of current use.

The term flavor ingredient as used herein is deemed to define a variety of flavor materials of both natural and synthetic origin. They include single compounds and mixtures. The system of the invention may encapsulate volatile or labile components which may be in liquid or solid form, preferably hydrophobic. Specific examples of such components may be found in the current literature, e.g. in Perfume and Flavour Chemicals by S. Arctander, 1969, Montclair N.J. (USA); Fenaroli's Handbook of Flavour Ingredients, 1975, CRC Press or Synthetic Food Adjuncts, 1947, by M. B. Jacobs, van Nostrand Co., Inc.

Suitable natural extracts which can be encapsulated for use in the present invention include citrus extracts such as lemon, orange, lime, grapefruit or mandarin oils; berry and currant extracts such as blackcurrant, raspberry and strawberry; cocoa, mint and vanilla essences; and essential oils of herbs or spices.

The proportion of flavor ingredient in the encapsulating matrix is preferably comprised between 0.1 and 25% by weight relative to encapsulated flavorant, and preferably between 5 and 16%. An emulsifier agent may suitably be present, in proportions varying typically from 0.1 to 10%, and preferably from 0.4 to 2%, relative to the solid product. Typical examples include soya lecithin and citric acid esters of fatty acids, but other suitable emulsifiers are cited in reference texts such as Food Emulsifiers and Their Applications, 1997, edited by G. L. Hasenhuettl and R. W. Hartel, USA.

One encapsulation technology employs small amounts of agar-agar, e.g. 1-7%, in combination with a carbohydrate material, in the composition of the matrix of an extruded system. The carbohydrate material used in combination with agar-agar can be any sugar or sugar derivative which can be readily processed through extrusion techniques to form a dry extruded solid. Particular examples of suitable materials include those selected from the group consisting of sucrose, glucose, lactose, levulose, fructose, maltose, ribose, dextrose, isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol, pentatol, arabinose, pentose, xylose, galactose, hydrogenated starch hydrolysate or succinylated, chemically modified starch, corn syrup, maltodextrin, polydextrose and derivatives and mixtures thereof. In one particular embodiment of the invention the carbohydrate material is selected from the group consisting of maltodextrin or a corn syrup, a chemically modified starch, a hydrogenated starch hydrolysate or a succinylated or hydrolyzed starch. Preferably, the maltodextrin used has a dextrose equivalent (DE) of at least 18. In specific embodiments, there will be used polymeric carriers which include maltodextrin. The latter can be the main carbohydrate material of the matrix, or yet, be used in admixture with any one of the sugars mentioned above, preferably sucrose.

In another approach a colloid gel may first be formed by dissolving gelatin in water at an appropriate temperature. This temperature is usually determined by the gelling temperature of the selected gelatin or other polymers. The mixture is mixed with a high sheer mixer such as Breddo Likwifier (American Ingredients Co., 550 South 18th St., Kansas City, Kans. 66105-1104) to dissolve the gelatin completely. This mixture turns into a very viscous gel.

Flavor oil is added while the gel is being mixed. Mixing is continued until the core materials are thoroughly dispersed uniformly in the gel matrix. In some situations, the colloid gel may need two or more gelling polymers to obtain the desired properties of the gel matrix. The flavor oil stays in the gel matrix with reasonable stability due to the character of the gel matrix and the hydrophobic and hydrophilic nature of gel polymers. This colloidal gel matrix can be used in the gel form. Flavor oil is encapsulated in the gel matrix, which can be ground and mixed into the tabletting formulation.

A base formulation was developed to see if it was even possible to make tablet that was swallowable and would disintegrate rapidly in a glass of hot or warm water, to provide a drink of volume in the range 50-150 ml; preferably 80-120 ml. This was attempted using a directly-compressible grade of paracetamol which is coated with pre-gelatinized starch; together with phenylephrine (hydrochloride), magnesium stearate, microcrystalline cellulose and crospovidone; and producing a caplet-shaped tablet by a standard tabletting method.

Ingredient Weight Paracetamol PGS 500 mg Phenylephrine HCl 6.1 mg (URT aid) Microcrystalline cellulose 80 mg (binder) Crospovidone 80 mg (disintegration aid) Magnesium stearate 6 mg (pressing aid) Total: 672.1 mg

A large number of spray-dried lemon flavors were obtained from suppliers and a satisfactory lemon flavor was obtained when these were added to the tablet mixes along with aspartame (38 mg) and citric acid (50 mg). However in every case the tablet mixes failed to tablet satisfactorily. The cause is believed to be a flavor oil released from the flavor under compressive loading, preventing the powder from binding satisfactorily.

It was apparent that an alternate flavoring technology would be required, one in which the oil would not be released under compression. 122 mg of a proprietary encapsulated lemon flavorant per tablet was used and it was found that this material did not affect the ability to tablet the mixed powders. A proprietary encapsulated blackcurrant flavorant also tabletted satisfactorily.

The use of an encapsulated flavorant permits the tabletting of flavorant oils at relatively high loading which was not possible before in a tablet weighing approximately 1 g.

Formulated examples are now given, by way of illustration.

Lemon Tablet Example 1

Ingredient mg/tab Paracetamol DC PGS 529 Guafenesin 100 Phenylephrine hydrochloride 450 6 Encapsulated flavorant 122 Avicel PH101 100 Crospovidone 100 Citric acid anhyd. 50 Aspartame 38 Magnesium Stearate 12 Yellow coloring agent 5 Total: 1062 mg

Lemon Tablet Example 2

Ingredient mg/tab Paracetamol DC PGS 529 Phenylephrine hydrochloride 450 6 Encapsulated flavorant 122 Avicel PH101 80 Crospovidone 80 Citric acid anhyd. 50 Aspartame 38 Magnesium Stearate 6 Yellow coloring agent 5 Total: 916 mg

It was found that both examples were excellent in terms of tabletting; in mechanical properties (including hardness and friability); in mouthfeel and taste when taken in the mouth as a tablet; in dissolution speed into warm or hot water to make a drink; in taste when thus dissolved, and drunk; and in cosmetic properties (including appearance and surface finish).

Lemon tablet Example 2 (three batches, 2A, 2B and 2C) was subjected to friability testing using the standard method of Ph Eur monograph, method 2.9.7. (10 tablets, 100 drops over 4 minutes, loss of tablet weight to abrasion determined. Percentage loss calculated giving friability value). It was further subjected to hardness testing using the standard method of Ph Eur monograph, method 2.9.8. (10 tablets, assessing resistance to crushing under diametrical loading). The results are shown on the following table, as Samples 2A, 2B and 2C.

In the table the time—0 mins, 15 mins, 30 mins, 150 mins—denotes when in a production run tablets were removed for testing. Samples 2A, 20 tablets in number, were taken out for a first production run at the stated times and were weighed, and the average weights calculated. These values are given in the first column headed 2A. 10 tablets were then subjected to the friability testing and the weight loss values are shown. The remaining 10 tablets were subjected to hardness testing and the mean compressive force at which failure takes place are shown.

The regime of testing was repeated with Sample 2B and Sample 3C and the results are again shown in the table.

In general it may be stated that tabletting gave a good consistency of tablet weight; that the friability of the tablets was low; and that the tablets were moderately hard. This is good in terms of robustness in manufacture and handling but also good in terms of speed dissolution. It is believed that a hard tablet promotes fast dissolution. On our dissolution tests it was observed that dissolution of the tablets in hot water was extremely fast: typically 70% of the paracetamol is released into hot water in the first 40 seconds of dissolution; and substantially all of it in the first minute.

Sample Mean Tablet Weight/Mg Friability/% Hardness/Kp Mins 2A 2B 2C 2A 2B 2C 2A 2B 2C 0 0.9086 0.9233 0.9170 0.27 0.27 0.22 15.26 16.41 18.98 15 0.9148 0.9117 0.9224 0.22 0.26 0.24 15.66 16.19 15.64 30 0.9176 0.9171 0.9222 0.21 0.27 0.23 15.97 16.36 15.26 45 0.9132 0.9187 0.9194 0.26 0.27 0.23 15.97 17.23 16.42 60 0.9234 0.9188 0.9224 0.24 0.27 0.26 16.42 17.14 15.95 75 0.9107 0.9260 0.9244 0.24 0.26 0.25 16.30 17.18 15.96 90 0.9230 0.9275 0.9214 0.23 0.24 0.26 15.89 17.10 16.42 105 0.9227 0.9100 0.9195 0.25 0.24 0.23 16.84 16.15 15.99 120 0.9230 0.9130 0.9182 0.25 0.26 0.23 15.97 14.92 16.57 135 0.9158 0.9081 0.9136 0.26 0.28 0.26 16.42 14.81 16.27 150 0.9085 0.9165 0.9076 0.25 0.25 0.24 16.50 15.82 16.01

Numerous characteristics and advantages have been set forth in the foregoing description, together with details of structure and function. While the invention has been disclosed in several forms, it will be apparent to those skilled in the art that many modifications, additions, and deletions, especially in matters of shape, size, and arrangement of parts, can be made therein without departing from the spirit and scope of the invention and its equivalents as set forth in the following claims. Therefore, other modifications or embodiments as may be suggested by the teachings herein are particularly reserved as they fall within the breadth and scope of the claims here appended. 

What is claimed is:
 1. A medicament tablet comprising: paracetamol; and an encapsulated flavorant.
 2. The tablet of claim 1 comprising from 200-800 mg of paracetamol.
 3. The medicament tablet of claim 1 further comprising a disintegration aid; wherein the tablet is suitable to be swallowed in tablet form, but also disperses or dissolves in water to produce a palatable drink.
 4. The medicament tablet of claim 1 further comprising a URT aid selected from the group consisting of dextromethorphan, noscapine, ethyl morphine, theobromine, pholcodine, codeine, oxymetazoline, phenylephrine, pseudoephedrine, diphenhydramine, guaifenesin and ambroxol.
 5. The medicament tablet of claim 1 further comprising another analgesic medicament selected from the group consisting of ibuprofen, flurbiprofen, buprenorphine, aspirin, codeine, celecoxib, diclofenac, ketoprofen, meloxicam, naproxen and rofecoxib.
 6. The tablet of claim 3, wherein the disintegration aid comprises a water-swellable polymer.
 7. The tablet of claim 3 comprising from 20-200 mg of the disintegration aid.
 8. The tablet of claim 6, wherein the water-swellable polymer comprises crospovidone.
 9. A medicament tablet comprising: from 200-800 mg of paracetamol; an encapsulated flavorant; from 20-200 mg of a disintegration aid; a URT aid selected from the group consisting of dextromethorphan, noscapine, ethyl morphine, theobromine, pholcodine, codeine, oxymetazoline, phenylephrine, pseudoephedrine, diphenhydramine, guaifenesin and ambroxol; and another analgesic medicament selected from the group consisting of ibuprofen, flurbiprofen, buprenorphine, aspirin, codeine, celecoxib, diclofenac, ketoprofen, meloxicam, naproxen and rofecoxib; wherein the tablet is suitable to be swallowed in tablet form, but also disperses or dissolves in water to produce a palatable drink.
 10. The tablet of claim 9, wherein the disintegration aid comprises a water-swellable polymer.
 11. The tablet of claim 10, wherein the water-swellable polymer comprises crospovidone.
 12. A medicament tablet comprising: paracetamol; encapsulated flavorant; disintegration aid; binder; pressing aid; organic acid/salt flavorant; and sweetening agent.
 13. The tablet of claim 12, wherein the tablet weight is within a weight range of from 700 to 1400 mg, and wherein the tablet has the following characteristics: its friability does not exceed 2% as determined by Ph Eur monograph method 2.9.7; its hardness is in the range 8-26 kp as determined by Ph Eur monograph method 2.9.8; it is palatable when taken as a tablet; and it dissolves quickly in water to produce a palatable drink.
 14. The tablet of claim 12, wherein the components comprise the following weight ranges: Component Weight Range (mg) paracetamol 200-800  encapsulated flavorant 40-240 disintegration aid 20-200 binder 20-200 pressing aid 2-50 organic acid/salt flavorant 10-100 sweetening agent 10-80 


15. The tablet of claim 14, wherein the tablet weight is within a weight range of from 700 to 1400 mg, and wherein the tablet has the following characteristics: its friability does not exceed 2% as determined by Ph Eur monograph method 2.9.7; its hardness is in the range 8-26 kp as determined by Ph Eur monograph method 2.9.8; it is palatable when taken as a tablet; and it dissolves quickly in water to produce a palatable drink.
 16. A method of making the tablet of claim 1 comprising compressing paracetamol and an encapsulated flavorant.
 17. The method according to claim 16, wherein the form of paracetamol and encapsulated flavorant is each individually selected from the group consisting of powder and granules.
 18. The method according to claim 17 comprising a direct tabletting method.
 19. The method according to claim 17, wherein the method does not include a heating or warming step.
 20. The method according to claim 17, wherein the method does not include wet granulation.
 21. The method according to claim 17, wherein the method includes the addition of the encapsulated flavorant substantially at the stage when paracetamol is mixed with any other ingredients that may be present. 